OBJECTIVE To determine the nature of the MHC class I loci in New World Primates. RESULTS Homologues of the human major histocompatibility complex (MHC) HLA-A, -B, -E, -F, and -G loci are present in all the Catarrhini (Old World primates, apes, and humans), and some of their allelic lineages have survived several speciation events. Analysis of 26 MHC class I cDNAs from seven different genera of New World primates revealed that the Callitrichinae (tamarins and marmosets) are an exception to these rules of MHC stability. In gene trees of primate MHC class I genes, sequences from the Callitrichinae cluster in a genus-specific fashion, whereas in the other genera of New World primates, as in the Catarrhini, they cluster in a transgeneric way. DISCUSSION The genus-specific clustering of the Callitrichinae cDNAs indicates that there is no orthology between MHC class I loci in genera of this phyletic group. Additionally, the Callitrichinae genera exhibit limited variability of their MHC class I genes, in contrast to the high variability displayed by all other primates. Each Callitrichinae genus, therefore, expresses its own set of MHC class I genes, suggesting that an unusually high rate of turnover of loci occurs in this subfamily. The limited variability of MHC class I genes in the Callitrichinae is likely the result of the recent origin of these loci. FUTURE DIRECTIONS These data will facilitate an understanding of the immunogenetics of New World Primates. Several of these species are important animal models for human diseases (i.e. ulcerative colitis and multiple sclerosis). KEY WORDS MHC, 1D IEF, PBL FUNDING NIH RR00167, DK44886 PUBLICATIONS Cadavid, LF, Shufflebotham, C, Ruiz, FJ, Yeager, M, Hughes, AL, and D.I. Watkins. 1998. Unusual post-species evolution of the MHC class I loci in New World primates. Proc. Natl. Acad. Sci., USA 94:14536-14541.